SNP Browser for Human [Homo sapiens] Genetic Disorders

DiseaseID	HGD14
Genetic Disorder	Rett syndrome
Gene Name	MeCP2
Description	Rett syndrome (RTT) is a progressive neurodevelopmental disorder almost exclusively affecting females. With an incidence of about 1 in 10,000 births, it is a common cause of profound mental impairment in girls. Typically, babies with RTT develop normally until the age of 6 to 18 months, when their developmental milestones regress. They lose purposeful use of their hands and are seriously disabled for life, with reduced muscle tone and seizures. A temporary "autistic-like" phase often occurs at the onset of the disorder, and older children are known for their social engagement through intense eye gaze. RTT is caused by mutations in the gene MeCP2, found on the X chromosome. MeCP2 is called a "transcriptional repressor" because it codes for a protein that controls the expression of other genes. Depending on what part of the gene contains the mutation, partial loss of this protein changes the environment experienced by developmentally important proteins which, in turn, leads to the RTT phenotype.
Symptoms	Rett syndrome is usually not apparent at birth. In fact, many infants appear to have normal development up until about age 6-18 months. For some children, the symptoms come on quickly, and parents can note specific dates when particular symptoms began. For other children, the changes come more slowly. As the child grows older, symptoms may include: • Normal head circumference at birth followed by slowing of the rate of head growth (can occur as early as 3 months of age) • Falling behind other children in the ability to do things like crawling, walking, or playing, or may lose the ability to do those things • Poor weight gain • Seizures may occur • Loss of the ability to talk and communicate • Repeated, stereotypical hand movements, such as hand wringing, clapping, washing, or hand-to-mouth movements • Biting, chewing, or swallowing difficulties; may grind teeth (bruxism) or have involuntary tongue movements • Muscle rigidity or spasms; walking is usually stiff-legged Other symptoms may include irregular breathing patterns, abnormal sleeping, or scoliosis
Causes	Rett syndrome occurs almost exclusively in girls and may be misdiagnosed as autism or cerebral palsy. Studies have linked 75% of Rett syndrome cases to a defect in the methl-CpG-binding protein 2 (MeCP2) gene. The gene associated with Rett syndrome is on the X chromosome. Females have two X chromosomes, so even when one has this significant defect, the other X chromosome provides enough normal protein for the child to survive. Males born with this defect do not have a second X chromosome to compensate for the problem. Therefore, the defect is usually lethal, leading to miscarriage , stillbirth , or very early death. Most cases of the defect occur without causes. However, there seem to be groups of the disease within families and certain geographic regions, for example Norway, Sweden, and northern Italy.
Diagnosis	Diagnosis of Rett syndrome is usually based on the symptoms the child has and the history of the child’s change in development. Not all of the symptoms are seen in every individual, and symptoms may range from mild to severe. Criteria (symptoms) required to make a diagnosis of Rett syndrome include: • Apparently normal development through at least the first 5-6 months of life • Normal head circumference at birth followed by slowing of the rate of head growth • Loss of acquired skills including language and communication • Loss of purposeful hand movements and the start of stereotypical hand movements • Difficulty walking (among those girls who can walk) • Shakiness of the torso and/or limbs There is a blood test which can identify the MECP2 gene mutation, but although testing positive for the mutation confirms the diagnosis of Rett syndrome, it is not required. The Rett Syndrome Research Foundation has specific information about MECP2 testing available online. There are, of course, many other disorders which may cause one or more of the symptoms seen in Rett syndrome. Therefore, other diagnostic tests may be done to exclude other disorders.
Treatment	There is no cure for Rett syndrome, so treatment focuses on managing the symptoms each individual has. Usually, this requires a team approach to maximize the individual’s abilities. If seizures are present, antiseizure medications may be given. Physical and occupational therapy help relieve muscle rigidity, improve motion of the joints, and prevent muscle contractures. Speech therapy can assist with communication and swallowing problems. A high-calorie diet may help with weight gain. Osteoporosis (weak bones) is common in individuals with Rett syndrome, so bone-strengthening medication (such as biophosphonate) and calcium supplements may be needed.